The objective of this proposal is to better define the role of activated macrophages in host resistance to cancer and intracellular infection. Our completed studies in mice show that prophylactic infection with intracellular protozoan parasites stimulates remarkable nonspecific resistance to autochthonous and transplanted tumors. Peritoneal macrophages from these mice are activated and are nonspecifically cytotoxic to tumorigenic cells in vitro. We now plan to use these in vivo and in vitro experimental models to determine: (1) if nonspecific resistance to neoplasia in mice can be stimulated by infection with intracellular protozoa or BCG after the graft of tumor cells, (2) if nonspecific resistance stimulated by Bacillus Calmette- Guerin (BCG) is mediated at the effector level by a population of activated macrophages that are nonspecifically cytotoxic to tumorigenic target cells in vitro, and (3) to better define nonspecific factors of host resistance and relate them to specific immune mechanisms, a profile of a number of immunologic and nonimmunologic parameters will be measured in normal and chronically infected mice. All studies are designed to lead to a better definition of nonspecific mechanisms in the homeostatic control of carcinogenesis and tumor growth.